Links to Exploration step
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Lymphatic Endothelial Heparan Sulfate Deficiency Results in Altered Growth Responses to Vascular Endothelial Growth Factor-C (VEGF-C)<xref ref-type="fn" rid="FN1">*</xref><xref ref-type="fn" rid="FN3"><sup><inline-graphic xlink:href="sbox.jpg"></inline-graphic></sup></xref><xref ref-type="fn" rid="FN2"><sup>♦</sup></xref></title><author><name sortKey="Yin, Xin" sort="Yin, Xin" uniqKey="Yin X" first="Xin" last="Yin">Xin Yin</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Johns, Scott C" sort="Johns, Scott C" uniqKey="Johns S" first="Scott C." last="Johns">Scott C. Johns</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Lawrence, Roger" sort="Lawrence, Roger" uniqKey="Lawrence R" first="Roger" last="Lawrence">Roger Lawrence</name><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Xu, Ding" sort="Xu, Ding" uniqKey="Xu D" first="Ding" last="Xu">Ding Xu</name><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Reddi, Krisanavane" sort="Reddi, Krisanavane" uniqKey="Reddi K" first="Krisanavane" last="Reddi">Krisanavane Reddi</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Bishop, Joseph R" sort="Bishop, Joseph R" uniqKey="Bishop J" first="Joseph R." last="Bishop">Joseph R. Bishop</name><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Varner, Judith A" sort="Varner, Judith A" uniqKey="Varner J" first="Judith A." last="Varner">Judith A. Varner</name><affiliation><nlm:aff id="aff4"></nlm:aff></affiliation></author><author><name sortKey="Fuster, Mark M" sort="Fuster, Mark M" uniqKey="Fuster M" first="Mark M." last="Fuster">Mark M. Fuster</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff id="aff4"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21343305</idno><idno type="pmc">3083229</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083229</idno><idno type="RBID">PMC:3083229</idno><idno type="doi">10.1074/jbc.M110.206664</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">002E88</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002E88</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Lymphatic Endothelial Heparan Sulfate Deficiency Results in Altered Growth Responses to Vascular Endothelial Growth Factor-C (VEGF-C)<xref ref-type="fn" rid="FN1">*</xref><xref ref-type="fn" rid="FN3"><sup><inline-graphic xlink:href="sbox.jpg"></inline-graphic></sup></xref><xref ref-type="fn" rid="FN2"><sup>♦</sup></xref></title><author><name sortKey="Yin, Xin" sort="Yin, Xin" uniqKey="Yin X" first="Xin" last="Yin">Xin Yin</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Johns, Scott C" sort="Johns, Scott C" uniqKey="Johns S" first="Scott C." last="Johns">Scott C. Johns</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Lawrence, Roger" sort="Lawrence, Roger" uniqKey="Lawrence R" first="Roger" last="Lawrence">Roger Lawrence</name><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Xu, Ding" sort="Xu, Ding" uniqKey="Xu D" first="Ding" last="Xu">Ding Xu</name><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Reddi, Krisanavane" sort="Reddi, Krisanavane" uniqKey="Reddi K" first="Krisanavane" last="Reddi">Krisanavane Reddi</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Bishop, Joseph R" sort="Bishop, Joseph R" uniqKey="Bishop J" first="Joseph R." last="Bishop">Joseph R. Bishop</name><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Varner, Judith A" sort="Varner, Judith A" uniqKey="Varner J" first="Judith A." last="Varner">Judith A. Varner</name><affiliation><nlm:aff id="aff4"></nlm:aff></affiliation></author><author><name sortKey="Fuster, Mark M" sort="Fuster, Mark M" uniqKey="Fuster M" first="Mark M." last="Fuster">Mark M. Fuster</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff id="aff4"></nlm:aff></affiliation></author></analytic><series><title level="j">The Journal of Biological Chemistry</title><idno type="ISSN">0021-9258</idno><idno type="eISSN">1083-351X</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Growth and remodeling of lymphatic vasculature occur during development and during various pathologic states. A major stimulus for this process is the unique lymphatic vascular endothelial growth factor-C (VEGF-C). Other endothelial growth factors, such as fibroblast growth factor-2 (FGF-2) or VEGF-A, may also contribute. Heparan sulfate is a linear sulfated polysaccharide that facilitates binding and action of some vascular growth factors such as FGF-2 and VEGF-A. However, a direct role for heparan sulfate in lymphatic endothelial growth and sprouting responses, including those mediated by VEGF-C, remains to be examined. We demonstrate that VEGF-C binds to heparan sulfate purified from primary lymphatic endothelia, and activation of lymphatic endothelial Erk1/2 in response to VEGF-C is reduced by interference with heparin or pretreatment of cells with heparinase, which destroys heparan sulfate. Such treatment also inhibited phosphorylation of the major VEGF-C receptor VEGFR-3 upon VEGF-C stimulation. Silencing lymphatic heparan sulfate chain biosynthesis inhibited VEGF-C-mediated Erk1/2 activation and abrogated VEGFR-3 receptor-dependent binding of VEGF-C to the lymphatic endothelial surface. These findings prompted targeting of lymphatic <italic>N</italic>-deacetylase/<italic>N</italic>-sulfotransferase-1 (Ndst1), a major sulfate-modifying heparan sulfate biosynthetic enzyme. VEGF-C-mediated Erk1/2 phosphorylation was inhibited in Ndst1-silenced lymphatic endothelia, and scratch-assay responses to VEGF-C and FGF-2 were reduced in Ndst1-deficient cells. In addition, lymphatic Ndst1 deficiency abrogated cell-based growth and proliferation responses to VEGF-C. In other studies, lymphatic endothelia cultured <italic>ex vivo</italic> from <italic>Ndst1</italic> gene-targeted mice demonstrated reduced VEGF-C- and FGF-2-mediated sprouting in collagen matrix. Lymphatic heparan sulfate may represent a novel molecular target for therapeutic intervention.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Biol Chem</journal-id><journal-id journal-id-type="hwp">jbc</journal-id><journal-id journal-id-type="pmc">jbc</journal-id><journal-id journal-id-type="publisher-id">JBC</journal-id><journal-title-group><journal-title>The Journal of Biological Chemistry</journal-title></journal-title-group><issn pub-type="ppub">0021-9258</issn><issn pub-type="epub">1083-351X</issn><publisher><publisher-name>American Society for Biochemistry and Molecular Biology</publisher-name><publisher-loc>9650 Rockville Pike, Bethesda, MD 20814, U.S.A.</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">21343305</article-id><article-id pub-id-type="pmc">3083229</article-id><article-id pub-id-type="publisher-id">M110.206664</article-id><article-id pub-id-type="doi">10.1074/jbc.M110.206664</article-id><article-categories><subj-group subj-group-type="heading"><subject>Cell Biology</subject></subj-group></article-categories><title-group><article-title>Lymphatic Endothelial Heparan Sulfate Deficiency Results in Altered Growth Responses to Vascular Endothelial Growth Factor-C (VEGF-C)<xref ref-type="fn" rid="FN1">*</xref><xref ref-type="fn" rid="FN3"><sup><inline-graphic xlink:href="sbox.jpg"></inline-graphic></sup></xref><xref ref-type="fn" rid="FN2"><sup>♦</sup></xref></article-title><alt-title alt-title-type="short">VEGF-C Responses Depend on Lymphatic Heparan Sulfate</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Yin</surname><given-names>Xin</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="aff" rid="aff2"><sup>§</sup></xref><xref ref-type="author-notes" rid="FN4"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Johns</surname><given-names>Scott C.</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="aff" rid="aff2"><sup>§</sup></xref><xref ref-type="author-notes" rid="FN4"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lawrence</surname><given-names>Roger</given-names></name><xref ref-type="aff" rid="aff3"><sup>¶</sup></xref></contrib><contrib contrib-type="author"><name><surname>Xu</surname><given-names>Ding</given-names></name><xref ref-type="aff" rid="aff3"><sup>¶</sup></xref></contrib><contrib contrib-type="author"><name><surname>Reddi</surname><given-names>Krisanavane</given-names></name><xref ref-type="aff" rid="aff2"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bishop</surname><given-names>Joseph R.</given-names></name><xref ref-type="aff" rid="aff3"><sup>¶</sup></xref></contrib><contrib contrib-type="author"><name><surname>Varner</surname><given-names>Judith A.</given-names></name><xref ref-type="aff" rid="aff4"><sup>‖</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fuster</surname><given-names>Mark M.</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="aff" rid="aff2"><sup>§</sup></xref><xref ref-type="aff" rid="aff4"><sup>‖</sup></xref><xref ref-type="corresp" rid="cor1"><sup>2</sup></xref></contrib><aff id="aff1">From<label>‡</label>Medicine and Research Services, Veterans Affairs San Diego Healthcare System, San Diego, California 92161,</aff><aff id="aff2">the<label>§</label>Division of Pulmonary and Critical Care, Department of Medicine, University of California San Diego, La Jolla, California 92037,</aff><aff id="aff3">the<label>¶</label>Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California San Diego, La Jolla, California 92093, and</aff><aff id="aff4">the<label>‖</label>University of California San Diego Moores Cancer Center, La Jolla, California 92093</aff></contrib-group><author-notes><corresp id="cor1"><label>2</label> To whom correspondence should be addressed: <addr-line>University of California San Diego, Dept. of Medicine and Veterans Affairs San Diego Healthcare System, 3350 La Jolla Village Dr., San Diego, CA 92161.</addr-line> Tel.: <phone>858-552-8585 (Ext. 7347)</phone>; E-mail: <email>mfuster@ucsd.edu</email>.</corresp><fn fn-type="equal" id="FN4"><label>1</label><p>Both authors contributed equally to this work.</p></fn></author-notes><pub-date pub-type="ppub"><day>29</day><month>4</month><year>2011</year></pub-date><pub-date pub-type="epub"><day>22</day><month>2</month><year>2011</year></pub-date><volume>286</volume><issue>17</issue><fpage>14952</fpage><lpage>14962</lpage><history><date date-type="received"><day>29</day><month>11</month><year>2010</year></date><date date-type="rev-recd"><day>7</day><month>2</month><year>2011</year></date></history><permissions><copyright-statement>© 2011 by The American Society for Biochemistry and Molecular Biology, Inc.</copyright-statement></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zbc01711014952.pdf"></self-uri><abstract><p>Growth and remodeling of lymphatic vasculature occur during development and during various pathologic states. A major stimulus for this process is the unique lymphatic vascular endothelial growth factor-C (VEGF-C). Other endothelial growth factors, such as fibroblast growth factor-2 (FGF-2) or VEGF-A, may also contribute. Heparan sulfate is a linear sulfated polysaccharide that facilitates binding and action of some vascular growth factors such as FGF-2 and VEGF-A. However, a direct role for heparan sulfate in lymphatic endothelial growth and sprouting responses, including those mediated by VEGF-C, remains to be examined. We demonstrate that VEGF-C binds to heparan sulfate purified from primary lymphatic endothelia, and activation of lymphatic endothelial Erk1/2 in response to VEGF-C is reduced by interference with heparin or pretreatment of cells with heparinase, which destroys heparan sulfate. Such treatment also inhibited phosphorylation of the major VEGF-C receptor VEGFR-3 upon VEGF-C stimulation. Silencing lymphatic heparan sulfate chain biosynthesis inhibited VEGF-C-mediated Erk1/2 activation and abrogated VEGFR-3 receptor-dependent binding of VEGF-C to the lymphatic endothelial surface. These findings prompted targeting of lymphatic <italic>N</italic>-deacetylase/<italic>N</italic>-sulfotransferase-1 (Ndst1), a major sulfate-modifying heparan sulfate biosynthetic enzyme. VEGF-C-mediated Erk1/2 phosphorylation was inhibited in Ndst1-silenced lymphatic endothelia, and scratch-assay responses to VEGF-C and FGF-2 were reduced in Ndst1-deficient cells. In addition, lymphatic Ndst1 deficiency abrogated cell-based growth and proliferation responses to VEGF-C. In other studies, lymphatic endothelia cultured <italic>ex vivo</italic> from <italic>Ndst1</italic> gene-targeted mice demonstrated reduced VEGF-C- and FGF-2-mediated sprouting in collagen matrix. Lymphatic heparan sulfate may represent a novel molecular target for therapeutic intervention.</p></abstract><kwd-group><kwd>Cell Surface Receptor</kwd><kwd>Endothelium</kwd><kwd>Growth Factors</kwd><kwd>Heparan Sulfate</kwd><kwd>Heparin-binding Protein</kwd></kwd-group><funding-group><award-group><funding-source id="CS100">National Institutes of Health</funding-source><award-id rid="CS100">P01-HL57345-11</award-id></award-group></funding-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/LymphedemaV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002E88 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 002E88 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= LymphedemaV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé=
|texte=
}}
| This area was generated with Dilib version V0.6.31. |  |